Sarcoidosis is a multiorgan granulomatus inflammatory disorder likely resulting from an exaggerated T-dell response in genetically susceptible individuals. African-Americans are more frequently and severely affected by Sarcoidosis yet few collections of African American patients exist. We however, have amassed a large, well phenotyped cohort of close to 3,000 Sarcoidosis patients, family members and controls on which to perform an extensive search of the genome to identify potential susceptibility loci. Specifically, this "Grand Opportunity" proposal will, using a unique and easily-accessible cohort, perform the first, and much needed, genome-wide association (GWA) scan in African Americans using the first and only commercially available genotyping product that results in adequate coverage (>85%) of the African genome. Because of the size of our cohort, we are poised to replicate our findings in an independent sample and therefore propose candidate genes and regions for further characterization. We can further characterize the population origin of these effects based on ancestry data already obtained. Finally, we will develop a bioinformatics tool for the repository and investigation of genetic data (e.g. single nucleotide polymorphisms, copy number variants, etc), genomic data (e.g. physical location, genic location, function, degree of conservation, etc), and statistical data from prior linkage, admixture and candidate gene association studies as well as this and other GWA studies. This project aligns with the goals of the GO mechanism in that we can begin immediately upon funding, the discoveries made herein will birth multiple follow-up studies, the database resource will allow our field to take the next step beyond association into pathway-based and bioinformatics-driven analyses and finally, we will stimulate the American research enterprise via the purchase of over $2M in domestically produced goods and services and the creation and retention of several biotech and administrative jobs. In sum, our extensive African American cohort and our genotyping, analysis and bioinformatics resources as well as the extensive experience of our team of experts in AA Sarcoidosis genetics make an experiment of this magnitude and scope very unlikely to be completed by any other group. PUBLIC HEALTH RELEVANCE: This project will fast-forward Sarcoidosis, and likely other granulomatus or inflammatory disorders, genetics research by 1) identifying and replicating association to genetic variants throughout the genome and 2) facilitating characterization of these effects using related statistical, genetics and genomics data. In addition, this project will generate extensive revenue for American biotech products and jobs.